Rectal Microbicides: New Hope for HIV and STD Prevention

Why we need rectal microbicides What is involved in development Where the research is What you can do to get involved Objectives

Men at risk High rates of condom use are difficult to maintain, as the rate of new HIV infections shows New data reveals reasons for concern: –UK: 48.8% UAI in the past year –US: 30% UAI (HIV - men in past year) STD rates confirm UAI prevalence

Women at risk In large US survey, 35% of women age report having had anal sex at some time in their life 32% of high-risk women reported anal sex in past 6 months (Gross et al, 2000)

What is a microbicide? Microbicides are substances that can reduce the transmission of HIV and other STD pathogens when applied vaginally and, possibly, rectally. They are not yet available. Currently, they are formulated as lubes, gels or creams applied with an applicator like those shown here

We need a product that is… Inexpensive Easily accessible (over the counter) Easy to use Safe, non-irritating Available in various forms (in lubes, suppositories, on condoms) Effective

What if we had a complete HIV toolkit? Prior to exposure Point of transmission Treatment Male and female condoms and lube ART to prevent perinatal transmission Clean injecting equipment Vaginal and rectal microbicides Cervical barriers Post-exposure prophylaxis (PEP) Improved antiretroviral therapy Treatment for opportunistic infections Basic care/nutrition Prevention for positives Education and behavior change Therapeutic vaccines Rights-focused behaviour change Voluntary counselling and testing STI screening and treatment Male circumcision Preventative Vaccines Pre-exposure prophylaxis (PREP)

Why vaginal microbicides? Women currently have no way to protect themselves when her partner won’t use a condom Women biologically more vulnerable to HIV –2-4 times more likely than men to get HIV from vaginal sex Women may be less able to assert their rights Current methods (abstinence, fidelity, and condom use) often require male consent, knowledge, or cooperation

Laboratory Testing 2-6 Years Phase 3 (efficacy) 2 to 4 Years Simultaneous studies in some cases: HIV+, penile & rectal safety 10 or more years 3 products 4 products 30+ products Phase 1 (safety) 1 to 6 Months Phase 2 (safety) Up to 2 Years 25 – 40 people people 3,000-10,000 people Vaginal Microbicide Research in 2005

How could microbicides work? Kill/inactivate/immobilize the virus Boost body’s natural defenses Prohibit viral entry by blocking fusion Inhibit viral replication Create a physical barrier or some combination of these approaches

Physiological Differences VaginaRectum Most of the epithelium is 40 cell layers thick Very fragile epithelium, 1 cell layer thick. Fewer CD4 cells than rectum More inflammatory cells under surface (CD4 receptors) Acidic pHAlkaline, rather than acidic pH Enclosed pouchOpen-ended tube

Anatomy 101

Research questions Infection – more to learn about anal intercourse and HIV infection Testing - What assays (tests) to measure impact? Distribution – how would it spread? Application Methods? Dosing – how much, what is acceptable? How does rectal shedding of HIV impact risk?

Laboratory research To learn more about: How HIV infection occurs in the rectum – what cells are most vulnerable The impact of intercourse on rectal tissue (trauma, inflammation, speed of healing) What markers can we look at to determine impact of a product on the rectum?

Laboratory research in action Dr. Ian McGowan, HPTN 056 University of California/Los Angeles Goal: To define measurements that can be made on rectal tissue biopsies that would be of use in rectal microbicide safety studies. Repeated measurements on 16 men, and studied variation based on: –Time –Location in the rectum –Sero status

Penile Acceptability Studies To learn more about… How much tissue is likely to be exposed to a microbicide Impact of a product on the penis

Distribution research in action: Dr. Craig Hendrix at Johns Hopkins University in Baltimore Volunteers simulated anal intercourse MRI scans done up to five hours after its release Initial studies suggest that semen could travel up to 60 centimeters Showed where a microbicide would be needed to protect vulnerable tissues

Behavioral Research To learn more about… Prevalence of anal intercourse for both mean and women – and how many of these acts are protected Preferences re: formulation and delivery systems Sexual practices that affect microbicide feasibility How much product is acceptable

Behavioral research in action: Alex Carballo-Diéguez, Columbia Univ (NY) Ken Mayer, Fenway Community Health (Boston) How much gel is tolerable? 18 HIV uninfected men Maximum acceptable dose for insertion and anal intercourse

Behavioral research in action: Alex Carballo-Diéguez and Sigma Research Center both did surveys of MSM interest in using microbicide Results: In San Francisco: 59% heard of microbicides, 25% - 35% might use (depending on stated effectiveness) In the UK: 23% had heard of microbicides, 59% might use

More vital steps 1.Men and women need education about the risks of unprotected anal sex 2.Safety trials on rectal application of vaginal microbicides that are currently in large scale trials 3.Testing over the counter lubes to see how safe they are 4.Advocacy for increased research

Rectal safety trials on vaginal products We won’t know if the first vaginal microbicides are effective for rectal use But we must know if they are safe to put in the rectum or not Because some people will try to use them rectally If deemed harmful for the rectum, labels warning against rectal use are imperative.

Testing on over the counter lubes Drs. Sudol & Phillips at Population Council, New York Tested 5 OTC lubes in mice to see if they caused damage to rectal cells KY-Plus (no longer on market) and DeLube caused the most damage Viamore, Vagisil and Astroglide caused some damage More research is underway, with findings expected soon. Need more research to see if these products cause damage to human rectal cells

Online Lube Survey 7,500 participants from 100 countries 700 women Data analysis by UCLA Information on condom and lubricant use, rectal microbicide acceptability Help establish priorities for testing lubes for rectal safety

Microbicide research is drastically under- funded Need for increased funding for both vaginal and rectal microbicides –Talk to your government officials –e.g., U.S. Microbicide Development Act Advocacy for rectal microbicides

Global Campaign for Microbicides A worldwide effort co-sponsored by groups working on HIV/AIDS reproductive health gay health women’s empowerment Working to educate, raise awareness and generate collective advocacy for increased political and public investment in microbicide development

New strategy to raise awareness and demand among gay men Three components: Internet – Public presence in forums & conferences Media – print, electronic, guerilla! LifeLube.org

International Rectal Microbicides Working Group Working Collaboratively: Global listserv Bi-monthly conference calls Developed an advocacy agenda To join, contact Jim Pickett, Presence at conferences: –Microbicides 2006 conference –Gay Men’s Health Conferences –Gay and Lesbian Medical Association annual meeting

What you can do Visit or to Join the International Rectal Microbicide Working Group calls and listserve Learn more about rectal microbicides Sign up for the Global Campaign’s newsletter Host a talk on microbicides – this and other presentations available for download Endorse the Global Campaign